Abstract Background: Bladder cancer in Egypt is the most prevalent malignancy among Egyptian males (16%), producing >7900 deaths annually, which is strikingly higher than most other parts of the world. The genesis and progression of urothelial bladder carcinoma (UBC) is known to involve alterations in several molecular pathways. Subtyping of bladder carcinoma patients based on the molecular alterations in their primary tumors may permit risk stratification and administration of more personalized therapies. Aim of Study: The aim of this study is to review the studies investigating the frequency of CK 5/6 expression and its value in the stratification of urothelial bladder carcinoma in English literature. Material and Methods: The data were retrieved from databases (PubMed, Medscape and Google scholar) and also material available on the Internet from 2001 till 2019. A structured systematic review was performed with the results tabulated. Results: The initial search presented 8 articles (2001- 2019). The frequency of CK 5/6 expression in UBC cases ranged between 19.7% and 62%. Positivity of CK 5/6 showed significant association with female gender, advanced tumor stage and pure SCC and UC with squamous differentiation. Positivity for CK 5/6 showed significant association with shorter overall survival in UC cases with squamous differen-tiation. CK5/6 expression alone was not associated with clinical outcome in any of the articles but showed significant association when combined with other markers. Conclusions: CK 5/6 as a basal marker could identify aggressive subtypes of urothelial carcinoma as those associated with squamous differentiation and advanced stage, however, it is not related to grading.